Effect of ramucirumab on ALBI grade in patients with advanced HCC: Results from REACH and REACH-2

Background & Aims: The albumin-bilirubin (ALBI) grade/score is derived from a validated nomogram to objectively assess prognosis and liver function in patients with hepatocellular carcinoma (HCC). In this post hoc analysis, we assessed prognosis in terms of survival by baseline ALBI grade and monitored liver function during treatment with ramucirumab or placebo using the ALBI score in patients with advanced HCC. Methods: Patients with advanced HCC, Child-Pugh class A with prior sorafenib treatment were randomised in REACH trials to receive ramucirumab 8 mg/kg or placebo every 2weeks. Datawere analysed by trial and as a meta-analysis of individual patientlevel data (pooled population) from REACH (alpha-fetoprotein>− 400 ng/ml) and REACH-2. Patients from REACHwith Child-Pugh class Bwere analysed as a separate cohort. The ALBI grades and scoreswere calculated at baseline and before each treatment cycle. Results: Baseline characteristics by ALBI grade were balanced between treatment arms among patients in the pooled population (ALBI-1, n = 231; ALBI-2, n = 296; ALBI-3, n = 7). Baseline ALBI grade was prognostic for overall survival (OS; ALBI grade 2 vs. 1; hazard ratio [HR]: 1.38 [1.13-1.69]), after adjusting for other significant prognostic factors. Mean ALBI scores remained stable in both treatment arms compared with baseline and were unaffected by baseline ALBI grade, macrovascular invasion, tumour response, geographical region, or prior locoregional therapy. Baseline ALBI grades 2 and 3 were associated with increased incidence of liver-specific adverse events and discontinuation rates in both treatments. Ramucirumab improved OS in patients with baseline ALBI grade 1 (HR 0.605 [0.445-0.824]) and ALBI grade 2 (HR 0.814 [0.630-1.051]. Conclusions: Compared with placebo, ramucirumab did not negatively impact liver function and improved survival irrespective of baseline ALBI grade

Pilot Scale Production of Highly Efficacious and Stable Enterovirus 71 Vaccine Candidates

BACKGROUND: Enterovirus 71 (EV71) has caused several epidemics of hand, foot and mouth diseases (HFMD) in Asia and now is being recognized as an important neurotropic virus. Effective medications and prophylactic vaccine against EV71 infection are urgently needed. Based on the success of inactivated poliovirus vaccine, a prototype chemically inactivated EV71 vaccine candidate has been developed and currently in human phase 1 clinical trial. PRINCIPAL FINDING: In this report, we present the development of a serum-free cell-based EV71 vaccine. The optimization at each step of the manufacturing process was investigated, characterized and quantified. In the up-stream process development, different commercially available cell culture media either containing serum or serum-free was screened for cell growth and virus yield using the roller-bottle technology. VP-SFM serum-free medium was selected based on the Vero cell growth profile and EV71 virus production. After the up-stream processes (virus harvest, diafiltration and concentration), a combination of gel-filtration liquid chromatography and/or sucrose-gradient ultracentrifugation down-stream purification processes were investigated at a pilot scale of 40 liters each. Although the combination of chromatography and sucrose-gradient ultracentrifugation produced extremely pure EV71 infectious virus particles, the overall yield of vaccine was 7-10% as determined by a VP2-based quantitative ELISA. Using chromatography as the downstream purification, the virus yield was 30-43%. To retain the integrity of virus neutralization epitopes and the stability of the vaccine product, the best virus inactivation was found to be 0.025% formalin-treatment at 37 °C for 3 to 6 days. Furthermore, the formalin-inactivated virion vaccine candidate was found to be stable for >18 months at 4 °C and a microgram of viral proteins formulated with alum adjuvant could induce strong virus-neutralizing antibody responses in mice, rats, rabbits, and non-human primates. CONCLUSION: These results provide valuable information supporting the current cell-based serum-free EV71 vaccine candidate going into human Phase I clinical trials

Performance of Sustainable Development and Technological Innovation Based on Green Manufacturing Technology of Artificial Intelligence and Block Chain

The powerful advanced manufacturing industry is the most powerful driving force for economic development and growth, and it is also the main source of environmental pollution. Artificial intelligence and blockchain technology are recognized as a breakthrough technology that can be widely used, changing the way the entire society and economy operate. The main constraints affecting the sustainable development of the manufacturing industry are ecological deterioration and resource shortage, but the development of artificial intelligence and blockchain technology provides new ideas for solving manufacturing problems. Based on this, this paper proposes a research on the sustainable development performance of green manufacturing technology innovation based on artificial intelligence and blockchain technology. This paper deeply grasps the essence and connotation of artificial intelligence and blockchain technology, analyzes its specific application form and research background, searches for the effective effect of manufacturing technology innovation and green manufacturing performance path, and clarifies the mechanism between the two. All measurement items in the questionnaire used in this article use Likert5 scale and use 1–5 options to indicate the degree of conformity with the actual situation of the enterprise. The results show that the average green manufacturing capacity of each measurement item is between 3.18∼3.97, indicating that the company's green manufacturing capacity is relatively high. Among them, the ability of green technology innovation is relatively high, indicating that most companies have noticed that the improvement of the ability of green technology innovation plays a vital role in the future sustainable development of enterprises. Moreover, more and more companies are paying attention to the latest applications of blockchain technology, which can effectively promote the development of enterprises

Grid-Side Current Improvement With Direct Digital Control and Capacitor Voltage Feedforward to Mitigate Distorted Grid Currents for 3Φ3W LCL Grid-Connected Inverter Under Distorted Grid Voltages

A three-phase three-wire LCL grid-connected inverter is usually used as an interface between renewable-energy sources and grid. However, grid voltage is always distorted and results in grid-current distortion when there is no control at the filter-capacitor current. This article presents the grid-current improvement with inverter-side-current direct digital control and capacitor voltage feedforward (CVF) for the grid-connected inverter under distorted grid voltages. With the inverter-side current feedback, the simple direct digital control can cover inductance variation and determine the control laws to track inverter-side inductor current, achieving robustness. A hysteresis repetitive predictor with finite impulse response low-pass filter and compensator term is introduced to the CVF loop which can stabilize the system and compensate the distorted grid current. The virtual impedance method is adopted to confirm the stability when the filter inductances drop and control parameters vary with the inductor current. Simulated and experimental results from 12 kW inverter are used to verify the theoretical analyses and discussions

Retina image–based optic disc segmentation

The change of optic disc can be used to diagnose many eye diseases, such as glaucoma, diabetic retinopathy and macular degeneration. Moreover, retinal blood vessel pattern is unique for human beings even for identical twins. It is a highly stable pattern in biometric identification. Since optic disc is the beginning of the optic nerve and main blood vessels in retina, it can be used as a reference point of identification. Therefore, optic disc segmentation is an important technique for developing a human identity recognition system and eye disease diagnostic system. This article hence presents an optic disc segmentation method to extract the optic disc from a retina image. The experimental results show that the optic disc segmentation method can give impressive results in segmenting the optic disc from a retina image

Identification of baicalin from Bofutsushosan and Daisaikoto as a potent inducer of glucose uptake and modulator of insulin signaling-associated pathways

Type 2 diabetes mellitus (T2DM) is a chronic disease characterized by hyperglycemia that can lead to long-term complications including heart diseases, stroke, retinopathy, and renal failure. Treatment strategies include stimulating glucose uptake and controlling blood glucose level. Bofutsushosan (BOF) and Daisaikoto (DAI) are two herb-based kampo medicines that have been demonstrated to improve metabolism-associated disorders including obesity, hyperlipidemia, and nonalcoholic fatty liver. Given their bioactivities against metabolic syndromes, we explored in this study the effect of BOF and DAI extracts on glucose absorption and used them as source to identify phytochemical stimulator of glucose absorption. Glucose uptake and mechanistic studies were evaluated in differentiated C2C12 skeletal muscle cells, and HPLC analysis was used to determine the molecular bioactive constituents. Our results indicated that the ethanolic extracts of BOF and DAI (BOFEE and DAIEE, respectively) enhanced the glucose uptake ratio in the differentiated C2C12 cells, and further analysis identified the flavone baicalin as a major constituent capable of efficiently stimulating glucose absorption. Mechanistic studies revealed that the effect from baicalin involved the activation of IRS-1 and GLUT-4, and implicated the AMPK, PI3K/Akt, and MAPK/ERK signaling cascades. Due to its potency, we suggest that baicalin merit further evaluation as a potential candidate anti-hyperglycemic agent for the treatment and management of T2DM. Keywords: Anti-hyperglycemia, Baicalin, Bofutsushosan, Daisaikoto, Glucose uptak